TY - JOUR
T1 - Reactions of 2,6-dimethyl-1,3-dioxane-4-ol (aldoxane) with deoxyguanosine and DNA
AU - Wang, M.
AU - McIntee, E. J.
AU - Cheng, G.
AU - Shi, Y.
AU - Villalta, Peter W
AU - Hecht, Stephen S
PY - 2001
Y1 - 2001
N2 - In a recent study, we identified several new DNA adducts of the carcinogen acetaldehyde, including N2-(2,6-dimethyl-1,3-dioxan-4-yl)deoxyguanosine (N2-aldoxane-dG, 2). Our goal in this study was to investigate further the formation of 2 by allowing 2,6-dimethyl-1,3-dioxane-4-ol (aldoxane, 5) to react with dG and DNA. Aldoxane is readily formed by trimerization of acetaldehyde. The reaction of aldoxane with dG and DNA produced diastereomers of N2-aldoxane-dG (2) as observed in the reactions of acetaldehyde with dG and DNA, supporting the intermediacy of aldoxane in their formation. Unexpectedly, however, an array of other adducts was formed in these reactions, including 3-(2-deoxyribos-1-yl)-5,6,7,8-tetrahydro-8-hydroxy-6-methylpyrimido[1,2- a]purine-10(3H)one (3), 2-amino-7,8-dihydro-8-hydroxy-6-methyl-3H-pyrrolo[2,1-f] purine-4(6H)one (13), N2-(3-hydroxybutylidene)dG (9), N2-[(2-hydroxypropyl)-6-methyl-1,3-dioxane-4-yl]dG (14), and N2-ethylidene-dG (1). Adduct 1 was the major product and was found to be quite stable in DNA. The adducts result from a cascade of aldehydes, e.g., 2-butenal (crotonaldehyde, 12), 3-hydroxybutanal (7) and its dimer (2-hydroxypropyl)-6-methyl-1,3-dioxane-4-ol (paraldol, 6), and acetaldehyde, produced from aldoxane under the reaction conditions. The reactions of aldoxane with dG and DNA were compared with those of paraldol. The paraldol reactions gave products resulting from reactions of dG and DNA with paraldol, 3-hydroxybutanal, and crotonaldehyde (adducts 3, 13, and 9) but the products of the aldoxane and acetaldehyde reactions (adducts 1 and 2) were not observed, indicating that paraldol is more stable under the reaction conditions than is aldoxane. The results of this study provide new insights about the formation of DNA adducts from aldehydes via condensation products of the latter.
AB - In a recent study, we identified several new DNA adducts of the carcinogen acetaldehyde, including N2-(2,6-dimethyl-1,3-dioxan-4-yl)deoxyguanosine (N2-aldoxane-dG, 2). Our goal in this study was to investigate further the formation of 2 by allowing 2,6-dimethyl-1,3-dioxane-4-ol (aldoxane, 5) to react with dG and DNA. Aldoxane is readily formed by trimerization of acetaldehyde. The reaction of aldoxane with dG and DNA produced diastereomers of N2-aldoxane-dG (2) as observed in the reactions of acetaldehyde with dG and DNA, supporting the intermediacy of aldoxane in their formation. Unexpectedly, however, an array of other adducts was formed in these reactions, including 3-(2-deoxyribos-1-yl)-5,6,7,8-tetrahydro-8-hydroxy-6-methylpyrimido[1,2- a]purine-10(3H)one (3), 2-amino-7,8-dihydro-8-hydroxy-6-methyl-3H-pyrrolo[2,1-f] purine-4(6H)one (13), N2-(3-hydroxybutylidene)dG (9), N2-[(2-hydroxypropyl)-6-methyl-1,3-dioxane-4-yl]dG (14), and N2-ethylidene-dG (1). Adduct 1 was the major product and was found to be quite stable in DNA. The adducts result from a cascade of aldehydes, e.g., 2-butenal (crotonaldehyde, 12), 3-hydroxybutanal (7) and its dimer (2-hydroxypropyl)-6-methyl-1,3-dioxane-4-ol (paraldol, 6), and acetaldehyde, produced from aldoxane under the reaction conditions. The reactions of aldoxane with dG and DNA were compared with those of paraldol. The paraldol reactions gave products resulting from reactions of dG and DNA with paraldol, 3-hydroxybutanal, and crotonaldehyde (adducts 3, 13, and 9) but the products of the aldoxane and acetaldehyde reactions (adducts 1 and 2) were not observed, indicating that paraldol is more stable under the reaction conditions than is aldoxane. The results of this study provide new insights about the formation of DNA adducts from aldehydes via condensation products of the latter.
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U2 - 10.1021/tx0100385
DO - 10.1021/tx0100385
M3 - Article
C2 - 11511176
AN - SCOPUS:0034865489
SN - 0893-228X
VL - 14
SP - 1025
EP - 1032
JO - Chemical research in toxicology
JF - Chemical research in toxicology
IS - 8
ER -